Sharma Ashish, Sahasrabudhe Vaishali, Musib Luna, Zhang Steven, Younis Islam, Kanodia Jitendra
Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut, USA.
Pfizer Inc., Groton, Connecticut, USA.
Clin Pharmacol Ther. 2022 Nov;112(5):946-958. doi: 10.1002/cpt.2489. Epub 2021 Dec 18.
Chronic kidney disease (CKD) is an important health issue that affects ~ 9.1% of the world adult population. Serum creatinine is the most commonly used biomarker for assessing kidney function and is utilized in different equations for estimating creatinine clearance or glomerular filtration rate (GFR). The Cockcroft-Gault formula for adults and "original" Schwartz formula for children have been the most commonly used equations for estimating kidney function during the last 3-4 decades. Introduction of standardized serum creatinine bioanalytical methodology has reduced interlaboratory variability but is not intended to be used with Cockcroft-Gault or original Schwartz equations. More accurate equations (for instance, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for adults and bedside Schwartz or Chronic Kidney Disease in Children Schwartz equation for children) based on standardized serum creatinine values (and another biomarker-cystatin C) have been introduced and validated in recent years. Recently, the CKD-EPI equation refitted without a race variable was introduced. Clinical practice guidance in nephrology advocates a shift to these equations for managing health care of patients with CKD. The guidance also recommends use of albuminuria in addition to GFR for CKD diagnosis and management. Significant research with large data sets would be necessary to evaluate whether this paradigm would also be valuable in drug dose adjustments. This article attempts to highlight some important advancements in the field from a clinical pharmacology perspective and is a call to action to industry, regulators, and academia to rethink the current paradigm for assessing kidney function to enable dose recommendation in patients with CKD.
慢性肾脏病(CKD)是一个重要的健康问题,影响着全球约9.1%的成年人口。血清肌酐是评估肾功能最常用的生物标志物,并被用于不同的公式来估算肌酐清除率或肾小球滤过率(GFR)。在过去三四十年里,成人用的Cockcroft-Gault公式和儿童用的“原始”Schwartz公式一直是估算肾功能最常用的公式。标准化血清肌酐生物分析方法的引入减少了实验室间的差异,但并不适用于Cockcroft-Gault公式或原始Schwartz公式。近年来,基于标准化血清肌酐值(以及另一种生物标志物——胱抑素C)的更准确的公式(例如,成人用的慢性肾脏病流行病学协作组(CKD-EPI)公式和儿童用的床边Schwartz公式或儿童慢性肾脏病Schwartz公式)已被引入并得到验证。最近,引入了不包含种族变量的重新拟合的CKD-EPI公式。肾脏病学的临床实践指南提倡转向使用这些公式来管理CKD患者的医疗保健。该指南还建议在CKD的诊断和管理中,除了GFR之外,还应使用蛋白尿。需要进行大量数据集的重要研究,以评估这种模式在药物剂量调整中是否也有价值。本文试图从临床药理学的角度突出该领域的一些重要进展,并呼吁行业、监管机构和学术界重新思考当前评估肾功能的模式,以便能够为CKD患者推荐剂量。